1. Field of the Invention
The invention relates to the field of therapeutic treatment of skin or tissue by exposure to light or other electromagnetic radiation in combination with cryogen cooling of the irradiated tissue.
2. Description of the Prior Art
An important issue in laser treatment of cutaneous lesions is to protect the epidermis from thermal damage. This heating, which is primarily caused by light absorption in the melanosomes, can easily bring the temperature of the basal layer above the threshold damage value of 65-70° C. Precooling of the epidermal basal layer from the normal value of 35° C. to 0° C. increases the optical radiant exposure that can be safely delivered by a factor of two.
Selective epidermal cooling can be obtained by exposing the skin surface to a cryogen for an interval of time corresponding to the thermal diffusion time from the stratum corneum through the epidermis and down to the basal layer. Thus, the upper layers are cooled while leaving the temperature of dermal and subcutaneous layers unchanged. Currently, selective epidermal cooling is achieved using a liquid spray of the cryogen R-134a (tetrafluoroethane) for 30-100 ms immediately before laser exposure. A typical procedure is to spray the surface for 30-50 ms, and then expose the skin to laser irradiation 20-30 ms after the end of the cryogen spurt.
Tetrafluoroethane (H2FC—CF3) is a chlorine free hydrofluorocarbon (HFC), thus representing no damage to the ozone layer. However, recent studies suggested that the non-CO2 greenhouse gases such as methane (CH4), nitrous oxide (N2O), hydrofluorocarbon (HFC), perfluorocarbon (PFC) and sulphur hexafluoride (SF6)) can make a significant contribution to global warming in comparatively low concentrations.
Table 1 gives the global warming potential (GWP) for frequently used gases. (The GWP of CO2 is defined as unity)
TABLE 1Major GWP Gases in the United States (100-year globalwarming potentials)aAtmosphericGasGWPLifetimeSource of EmissionsHFC-2311,700264HCFC-22 Production,Fire ExtinguishingEquipment,Aerosols, SemiconductorManufactureHFC-43-10mee1,30017.1SolventsHFC-1252,80032.6Refrigeration/AirConditioningHFC-134a1,30014.6Refrigeration/AirConditioning, Aerosols,FoamsHFC-143a3,80048.3Refrigeration/AirConditioningHFC-152a1401.5Refrigeration/AirConditioning, Aerosols,FoamsHFC-227ea2,90036.5Aerosols, FireExtinguishing EquipmentHFC-236fa6,300209Refrigeration/AirConditioning, FireExtinguishingSF623,9003,200ElectricityTransmission/Distribution;MagnesiumProduction;SemiconductorManufacturingPFCs6,500-9,20010,000-50,000Aluminum Smelting,(primarilySemiconductorCF4, C2F6)Manufacture,Fire ExtinguishingPFC/PFPEsb7,4003,200SolventsaNote that this table lists major commercial gases and sources; other minor gases and uses such as lab applications are not listed here. The GWPs and atmospheric lifetimes are taken from Climate Change 1995, the IPCC Second Assessment Report.bPFC/PFPEs are a diverse collection of PFCs and perfluoropolyethers (PFPEs) used as solvents.
Tetrafluoroethane R-134a, which is non-toxic, non-flammable, and non-ozone depleting, has a boiling point (b.p.) of −26° C. at 1 atm. These properties make it an excellent choice for cryogen spray cooling of human skin. However, R-134a has a comparatively high GWP of 1,300. Therefore, substitutes for R-134a for use in large scale applications such as air conditioners for cars, home appliances and manufacturing of thermally insulating polystyrene foams are being developed. As a result, carbon dioxide based air conditioners are being introduced for the car industry and non-fluorinated, but flammable, gases are used in home appliances today. The lowest GPW value (GWP=140) in table 1 is that of R152a (difluoroethane, F2HC—CH3), but this compound autoignites at 455° C.
The GWP values for non-fluorinated hydrocarbons such as propane (C3H8, R-290, b.p. −42.1° C.), butane (C4H10, R-600, b.p −0.5° C.) and isobutene (R-600a, b.p −12° C.) are very low because they are rapidly broken down in the atmosphere. The global warming potential of propane is GWP=3 and that of butane is less than 10.
Potential non-flammable candidates for cryogen spray cooling could be carbon dioxide (CO2, R-744) or nitrous oxide (N2O, R-744a) but, unfortunately, these compounds do not form boiling liquids at atmospheric pressure. Liquid CO2 results in dry-ice formation immediately after leaving the outlet nozzle. The skin surface will therefore be covered with a layer of dry-ice crystals. Possible reduction in the heat transfer coefficient due to build up of a porous layer of dry ice crystals can be avoided by having an adequate high momentum flux of the spray.
Liquid nitrogen (N2, b.p. −90° C.) is an environmentally safe, non-toxic and liquid forming cryogen which has been extensively used in dermatology. However, the evaporation loss is high, and the cryogenic equipment for delivering liquid cryogen spurts in the 100 ms range might be technically very cumbersome.
Interesting candidates are also in the group of flammable hydrocarbons, which are used today in medical applications. The commercial product Histofreezer®, which is used for the treatment of cervical bleeding and removal of warts, is composed of a mixture of dimethyl ether (C2H6O, b.p. −22° C.), propane and isobutene. Further on, these compounds are also used as propellants for hair lacquers, etc.
The use of a flammable cryogen during laser exposure for, e.g., hair removal requires special precautions. The pulse energy, which typically can be in the range of 20-70 J/cm2, can ignite the hair above the skin surface. Thus, the combined use of flammable cryogen and high laser energy might induce burns to the skin.
The dynamic cooling principle as defined in U.S. Pat. No. 5,814,040, which is incorporated herein by reference, represents a simple, reliable and efficient method for protection of the epidermis, and for some applications such as pulsed laser treatment of port wine stain lesions it represents the only choice for efficient protection. Port wine stain is a congenital lesion with a frequency of one in two hundred births, often resulting in a high psychological burden for the child.
What is needed is to find an efficient substitute for tetrafluoroethane that is compatible with requirements for low global warming potential.